Essa Pharma: Masofaniten, enzalutamide continue to be well tolerated

ESSA Pharma announced the presentation of updated dose escalation data from its Phase 1/2 study evaluating masofaniten, formerly EPI-7386, in combination with enzalutamide at the 2024 ASCO Genitourinary Cancers Symposium, taking place January 25 – 27, 2024, in San Francisco, CA. Masofaniten is a first-in-class N-terminal domain androgen receptor inhibitor that suppresses androgen activity through a novel mechanism of action and is being developed for the treatment of prostate cancer. This Phase 1/2 multicenter, open-label clinical trial enrolled patients with mCRPC who have received androgen deprivation therapy and who are naive to second-generation antiandrogens but may have been treated previously with one line of prior chemotherapy in the metastatic hormone-sensitive prostate cancer setting. The data presented today include 18 patients across four cohorts in the Phase 1 dose escalation portion of the study. Masofaniten has no effect on enzalutamide exposure, thus allowing the use of full dose per label of enzalutamide in combination. Enzalutamide reduces masofaniten exposure but twice daily dosing of masofaniten appears to mitigate the reduction and maintains clinically relevant drug exposures.In patients evaluable for safety, masofaniten combined with enzalutamide, continues to be well-tolerated at the dose levels tested through 25 cycles of dosing in some patients. Most frequent adverse events were Grades 1 and 2, related to either AR inhibition or gastrointestinal tract irritation. In Cohort 4, one patient experienced a Grade 3 rash, which was observed immediately following administration of masofaniten combined with enzalutamide and deemed probably related, resulting in the expansion of the cohort from four to seven patients. No additional dose-limiting toxicities were observed, therefore the maximum tolerated dose was not reached. The recommended Phase 2 combination doses were identified as masofaniten 600 mg twice daily in combination with enzalutamide 160 mg once daily. In the patients evaluable for efficacy, rapid, deep and durable reductions in PSA were observed, regardless of previous chemotherapy status, including in patients who received lower than the full dose of enzalutamide. Across all dose cohorts, 88% of patients achieved PSA50, 81% of patients achieved PSA90, 69% of patients achieved PSA90 in less than 90 days, and 63% of patients achieved PSA less than0.2ng/mL. While the data for disease PSA progression are still maturing with a current median follow up of 11.1 months, the median time to PSA progression is at 16.6 months.The randomized, open-label, two arm, Phase 2 dose expansion portion of the study is underway and is designed to evaluate the combination of masofaniten and enzalutamide versus single agent enzalutamide in patients with mCRPC naive to second generation anti-androgens. The study is currently enrolling at approximately 25 sites in the USA, Canada and Australia. Expansion to European sites is in progress.